Article
Biochemistry & Molecular Biology
Kyung-Hwa Baek, Trong-Nhat Phan, Satish R. Malwal, Hyeryon Lee, Zhu-Hong Li, Silvia N. J. Moreno, Eric Oldfield, Joo Hwan No
Summary: SQ109 is an anti-tubercular drug candidate that has shown potent activity against protozoan parasites including Leishmania, Trypanosoma cruzi, and Toxoplasma gondii in vitro. It has demonstrated efficacy in mouse models of T. cruzi and T. gondii infections, but moderate efficacy in models of Trypanosoma brucei and Leishmania donovani infections. Metabolites of SQ109 also exhibit activity against protozoan parasites in vitro.
Article
Public, Environmental & Occupational Health
Gerardo Priotto, Jose R. Franco, Veerle Lejon, Philippe Buescher, Enock Matovu, Joseph Ndung'u, Sylvain Bieler, Dieudonne Mumba, Nick Van Reet, Paul Verle, Vincent Jamonneau, Pere P. Simarro, Augustin Kadima Ebeja, Dieudonne Sankara, Daniel Argaw Dagne
Summary: Rhodesiense human African trypanosomiasis is a lethal parasitic infection caused by Trypanosoma brucei rhodesiense and transmitted by tsetse flies in eastern and southern Africa. It accounts for approximately 5% of all cases of human African trypanosomiasis. Currently, there is no simple serological test for rhodesiense human African trypanosomiasis and diagnosis relies on microscopic confirmation of trypanosomes in samples of blood or other tissues.
BULLETIN OF THE WORLD HEALTH ORGANIZATION
(2023)
Article
Biochemistry & Molecular Biology
Clemens Hinteregger, Johanna Dolensky, Werner Seebacher, Robert Saf, Pascal Maeser, Marcel Kaiser, Robert Weis
Summary: 2,4-Diaminopyrimidines and (dialkylamino)azabicyclo-nonanes have activity against protozoan parasites. A series of fused hybrids were synthesized and tested in vitro against malaria tropica and sleeping sickness pathogens. The activities and selectivities of compounds strongly depended on the substitution pattern of both ring systems as well as the position of the nitrogen atom in the bicycles.
Article
Infectious Diseases
Arunima Goswami, Tirthankar Koley, Madhan Vishal Rajan, Pathak Madhuri, Neelam Upadhyay, Uddipan Das, Manoj Kumar, Abdul Samath Ethayathulla, Gururao Hariprasad
Summary: This study found that Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, which are protozoan parasites, cause leishmaniasis, Chagas disease, and sleeping sickness, respectively. It was found that PAF-AH is an inflammatory protein involved in the pathogenesis of these three infections, making it an attractive drug target.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Chemistry, Medicinal
Mohammad-Reza Delnavazi, Samad Nejad Ebrahimi, Abbas Hadjiakhoondi, Narguess Yassa
Summary: Seven undescribed sesquiterpene derivatives, Azerins A-G (3-6, 8, 14 and 15), along with known sesquiterpene phenols (1, 2 and 7) and sesquiterpene coumarins (9-13), were isolated from the roots of Dorema glabrum. Their structures were determined using NMR and MS techniques. The compounds were evaluated for their antiprotozoal and cytotoxic activities, and Azerin G (15) exhibited potent growth inhibitory activity against T. b. rhodesiense, while compounds 1, 4, 7, and 8 showed selective inhibitory effects on P. falciparum.
Article
Biochemistry & Molecular Biology
Adullah Alotaibi, Godwin U. Ebiloma, Roderick Williams, Ibrahim A. Alfayez, Manal J. Natto, Sameah Alenezi, Weam Siheri, Malik AlQarni, John O. Igoli, James Fearnley, Harry P. De Koning, David G. Watson
Summary: Ethanolic extracts of temperate zone propolis from the UK and Poland exhibited anti-trypanosomal activity, with compounds like naringenin 4 ',7-dimethyl ether and 4 '-methoxykaempferol showing the highest activity. Different compounds were isolated and characterized, showing varying levels of activity against drug-resistant strains of T. brucei and L. mexicana, without a clear structure-activity relationship observed. Multiple compounds from temperate propolis have anti-kinetoplastid activity.
Article
Chemistry, Medicinal
Karol R. Francisco, Ludovica Monti, Wenqian Yang, Hayoung Park, Lawrence J. Liu, Kaitlyn Watkins, Dilini K. Amarasinghe, Marianna Nalli, Carlos Roberto Polaquini, Luis O. Regasini, Antonio Eduardo Miller Crotti, Romano Silvestri, Lizandra Guidi Magalha, Conor R. Caffrey
Summary: Trypanosoma brucei is a parasitic protozoan that causes Human African Trypanosomiasis. A study evaluated the antitrypanosomal activity of curcuminoids and analogs against T. b. brucei and found that certain dibenzylideneacetone (DBA) compounds exhibited potent activity. Further research on DBA analogs identified compounds with low EC50 values and high selectivity indices. These findings suggest that DBAs could serve as a starting point for developing new small molecule therapies for HAT.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Nuria Llurba Montesino, Marcel Kaiser, Pascal Maeser, Thomas J. Schmidt
Summary: The antitrypanosomal activity of Salvia officinalis L. is mainly attributed to abietane-type diterpenes of the rosmanol/rosmaquinone group, which showed significant activity against Trypanosoma brucei rhodesiense.
Article
Biochemistry & Molecular Biology
George E. Magoulas, Pantelis Afroudakis, Kalliopi Georgikopoulou, Marina Roussaki, Chiara Borsari, Theano Fotopoulou, Nuno Santarem, Emile Barrias, Paloma Tejera Nevado, Julia Hachenberg, Eugenia Bifeld, Bernhard Ellinger, Maria Kuzikov, Irini Fragiadaki, Effie Scoulica, Joachim Clos, Sheraz Gul, Maria Paola Costi, Wanderley de Souza, Kyriakos C. Prousis, Anabela Cordeiro da Silva, Theodora Calogeropoulou
Summary: A library of novel ether phospholipid analogues was designed and synthesized, with compounds showing potent antiparasitic activity against different parasitic species. The structure-activity relationships of these compounds were studied, and a potential lead compound with broad spectrum antiparasitic activity was identified, laying a foundation for the development of improved derivatives to control neglected tropical diseases.
Article
Chemistry, Medicinal
William J. Robinson, Annie E. Taylor, Solange Lauga-Cami, George W. Weaver, Randolph Rj Arroo, Marcel Kaiser, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Kuldip Singh, Tanja Schirmeister, Adolfo Botana, Chatchakorn Eurtivong, Avninder S. Bhambra
Summary: Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense, with current therapy limitations and the need for further investigation. Novel anti-trypanosomal compounds show promising potential, providing scaffolds for future drug development targeting the disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Daniel G. Silva, Pim-Bart Feijens, Rik Hendrickx, An Matheeussen, Lucie Grey, Guy Caljon, Louis Maes, Flavio S. Emery, Anna Junker
Summary: This study identified the isoindolone ring as a scaffold for novel agents against Trypanosoma brucei rhodesiense and explored the structure-activity relationships of various aromatic ring substitutions. Compound 20 exhibited low nanomolar potency against T. b. rhodesiense with no toxicity against MRC-5 and PMM cell lines, showing potential as a new lead template for agents against T. b. rhodesiense. However, the compounds' solubility remains a limiting factor that needs to be addressed to further develop in vivo-active derivatives.
Article
Parasitology
Kanok Preativatanyou, Komson Chinwirunsirisup, Atchara Phumee, Pathamet Khositharattanakool, Sakone Sunantaraporn, Padet Siriyasatien, Jerome Depaquit
Summary: Autochthonous leishmaniasis in Thailand has become a public health concern, with an increasing number of new clinical cases. A study in southern Thailand found Asian new leishmaniasis and visceral leishmaniasis transmitted by sand flies, as well as a suspected novel trypanosoma species. These findings contribute to a better understanding of the transmission of leishmaniasis and the establishment of effective prevention and control measures.
Article
Parasitology
Limo William Kipkorir, Thuita Kibuthu John, Orindi Benedict Owino, Oidho John, Shivairo Robert, Masiga Daniel, Adung'a Vincent Owino
Summary: The study identified Trypanosoma brucei rhodesiense strains that cause acute and chronic infections in mice, highlighting the predominant role of strain-dependent factors in determining infection outcomes. Additionally, the strain KETRI 3928 had better establishment in tsetse flies compared to KETRI 3801, suggesting potential differences in transmission of strains causing chronic infections.
EXPERIMENTAL PARASITOLOGY
(2021)
Article
Infectious Diseases
Camino Gutierrez-Corbo, Barbara Dominguez-Asenjo, Yolanda Perez-Pertejo, Carlos Garcia-Estrada, Felio J. Bello, Rafael Balana-Fouce, Rosa M. Reguera
Summary: Diseases caused by trypanosomatids are a serious public health concern in low-income endemic countries. Leishmaniasis, caused by different species of Leishmania, can be transmitted to humans through the bite of infected sandflies. Sexual reproduction has been confirmed in these parasites, and the formation of hybrids can contribute to their virulence, drug resistance, and adaptation to the host immune system. This study investigates the capability of intraclonal and interspecies genetic exchange in Leishmania parasites and demonstrates the feasibility of obtaining hybrids between different tropisms. Ploidy analysis, kDNA content, growth rate, and infection capacity provide important insights into sexual reproduction in these parasites.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Feriannys Rivas, Carolina Del Marmol, Gonzalo Scalese, Leticia Perez-Diaz, Ignacio Machado, Olivier Blacque, Andrea Medeiros, Marcelo Comini, Dinorah Gambino
Summary: In this study, new multifunctional Ru(II) ferrocenyl compounds were designed and synthesized as potential agents against human African trypanosomiasis and leishmaniasis. These compounds showed in vitro activity against the parasites and demonstrated selectivity towards them.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Helio Nitta Matsuura, Sonia Malik, Fernanda de Costa, Morteza Yousefzadi, Mohammad Hossein Mirjalili, Randolph Arroo, Avninder S. Bhambra, Miroslav Strnad, Mercedes Bonfill, Arthur Germano Fett-Neto
MOLECULAR BIOTECHNOLOGY
(2018)
Article
Microbiology
Katrien Van Bocxlaer, Eric Gaukel, Deirdre Hauser, Seong Hee Park, Sara Schock, Vanessa Yardley, Ryan Randolph, Jacob J. Plattner, Tejal Merchant, Simon L. Croft, Robert T. Jacobs, Stephen A. Wring
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2018)
Article
Biochemistry & Molecular Biology
Sullivan Renouard, Cyrielle Corbin, Samantha Drouet, Barbara Medvedec, Joel Doussot, Cyril Colas, Benoit Maunit, Avninder S. Bhambra, Eric Gontier, Nathalie Jullian, Francois Mesnard, Michele Boitel, Bilal Haider Abbasi, Randolph R. J. Arroo, Eric Laine, Christophe Hano
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2018)
Article
Chemistry, Medicinal
Ketan C. Ruparelia, Keti Zeka, Taeeba Ijaz, Dyan N. Ankrett, Nicola E. Wilsher, Paul C. Butler, Hoon L. Tan, Sabahat Lodhi, Avninder S. Bhambra, Gerard A. Potter, Randolph R. J. Arroo, Kenneth J. M. Beresford
MEDICINAL CHEMISTRY
(2018)
Article
Microbiology
Gert-Jan Wijnant, Katrien Van Bocxlaer, Amanda Fortes Francisco, Vanessa Yardley, Andy Harris, Mo Alavijeh, Sudaxshina Murdan, Simon L. Croft
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2018)
Article
Medicine, Research & Experimental
Minshan Guo, Ke Wang, Ning Qiao, Vanessa Yardley, Mingzhong Li
MOLECULAR PHARMACEUTICS
(2018)
Article
Chemistry, Medicinal
Catherine Fagundez, Diver Sellanes, Stella Pena, Laura Scarone, Anna C. C. Aguiar, Juliana O. de Souza, Rafael V. C. Guido, Lindsay Stewart, Vanessa Yardley, Sabine Ottilie, Elizabeth A. Winzeler, Francisco-J. Gamo, Laura M. Sanz, Gloria L. Serra
ACS MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Biochemical Research Methods
David J. Clark, Catherine M. Moore, Marc Flanagan, Katrien Van Bocxlaer, Evangelia-Theophano Piperaki, Vanessa Yardley, Simon L. Croft, John Tyson, Sam P. Whitehouse, Jonathan O'Halloran, Sanjeev Krishna, Henry M. Staines
Review
Biochemical Research Methods
Randolph R. J. Arroo, Avninder S. Bhambra, Christophe Hano, Gulin Renda, Ketan C. Ruparelia, Meng F. Wang
Summary: Analysis of biochemical pathways involves using labelled precursors to monitor metabolic fate, with mass spectrometry and nuclear magnetic resonance as common monitoring tools.
PHYTOCHEMICAL ANALYSIS
(2021)
Article
Chemistry, Medicinal
William J. Robinson, Annie E. Taylor, Solange Lauga-Cami, George W. Weaver, Randolph Rj Arroo, Marcel Kaiser, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Kuldip Singh, Tanja Schirmeister, Adolfo Botana, Chatchakorn Eurtivong, Avninder S. Bhambra
Summary: Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense, with current therapy limitations and the need for further investigation. Novel anti-trypanosomal compounds show promising potential, providing scaffolds for future drug development targeting the disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Chatchakorn Eurtivong, Collin Zimmer, Tanja Schirmeister, Chutikarn Butkinaree, Rungroj Saruengkhanphasit, Worawat Niwetmarin, Somsak Ruchirawat, Avninder S. S. Bhambra
Summary: A virtual screening of a ChemBridge molecule collection identified two nitrogenous heterocyclic molecules (12 and 15) with potential dual inhibitory properties against trypanosomal cruzain and rhodesain cysteine proteases. Molecular dynamics simulations revealed that the molecules can occupy the binding sites and stabilize the protease complexes. Binding affinity calculations showed that the virtual hits have comparable affinities to other known inhibitors, making them promising scaffolds with dual inhibition properties.
MOLECULAR DIVERSITY
(2023)
Review
Biochemistry & Molecular Biology
Gael N. N. Neba Ambe, Carlo Breda, Avninder Singh Bhambra, Randolph R. J. Arroo
Summary: The importance of the circadian clock in maintaining human health is widely recognized. Dysregulated and dampened clocks may contribute to age-related diseases and metabolic syndrome. This review explores dietary compounds that have a positive impact on the circadian clock, particularly nobiletin, which shows promise as a chronotherapeutic agent.
Article
Microbiology
Gert-Jan Wijnant, Katrien Van Bocxlaer, Vanessa Yardley, Andy Harris, Sudaxshina Murdan, Simon L. Croft
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2018)
Article
Microbiology
Gert-Jan Wijnant, Katrien Van Bocxlaer, Vanessa Yardley, Sudaxshina Murdan, Simon L. Croft
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2017)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
